Targeting The AGE-RAGE Axis In Diabetes Associated Atherosclerosis
Funder
National Health and Medical Research Council
Funding Amount
$542,859.00
Summary
Based on extensive preliminary data we porpose that the AGE intercation with RAGE plays an important role in diabetes associated atherosclerosis. We will perform studies using a soluble form of the receptor RAGE which will trap AGEs in the blood and tissues and thus prevent diabetes related blood vessel damage. Furthermore, we will investigate if RAGE receptor on inflammatory cells such as macrophages plays a pivotal role in blood vessel injury in diabetes.
Markers Of Androgen Action, Genetic Variation And Prostate Cancer Risk
Funder
National Health and Medical Research Council
Funding Amount
$798,907.00
Summary
This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic va ....This proposal aim to follow up evidence from a number of studies that genetic and non-genetic markers of hormonal action in different periods of a man's life are associated with prostate cancer risk using a collection of three large, independent epidemiologic studies on prostate cancer named the Prostate Cancer Program. A principal objective is to collect exposure data on acne and digit ratio, and genotype cases and controls across the studies of the Prostate Cancer Program for common genetic variants in 4 candidate genes in the hormonal pathway. The established risk factors for prostate cancer are only age, race and family history. We anticipate that this project will cast light on the role of hormones in prostate cancer and that we will identify new markers of risk of prostate cancer and markers of disease aggressiveness. These outcomes will help us identifying men who are at risk for prostate cancer to target screening and surveillance, and plan prevention strategies. Furthermore, they will also form the basis for research on treatment targets.Read moreRead less
A Trial Of A Multidisciplinary, Group Based Intervention To Meet The Needs Of Men With Prostate Cancer
Funder
National Health and Medical Research Council
Funding Amount
$524,285.00
Summary
This study will test an innovative approach to meeting the physical and psychosocial needs of men with early stage prostate cancer using a randomised controlled trial. This novel approach involves a combination of individual and group-based consultations which encourages peer-to-peer support, promotes self-care and enhances appropriate multidisciplinary referrals and communication. It provides a new model of care for patients with chronic diseases that can be translated into clinical practice.
Circulating Low -molecular Weight AGEs In The Development And Progression Of Diabetic Complications
Funder
National Health and Medical Research Council
Funding Amount
$297,523.00
Summary
High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific rec ....High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetesRead moreRead less
Evaluation Of The Efficacy Of The Australian Mammographic Screening Program
Funder
National Health and Medical Research Council
Funding Amount
$504,096.00
Summary
BreastScreen Australia uses interim measures such as participation, small cancer detection and interval cancer rates to monitor the impact of the program on mortality. Using BreastScreen Victoria as a case study, we will estimate the direct impact of the program on mortality for screened women, addressing Cancer Australia's priority of 'Improving screening program outcomes to ensure that patients can be identified and treated appropriately and ensuring that screening services are effective'.
Massively Parallel Sequencing And PCR Optimised For DNA-based Diagnostics And Discovery
Funder
National Health and Medical Research Council
Funding Amount
$201,664.00
Summary
The next generation of medical diagnostics and discovery in disease research will involve the marriage of PCR, a tool used to amplify large amounts of DNA from small starting quantities, and �next generation� sequencing, a way to sequence lots and lots of DNA on a single instrument run. This study aims to describe methods which allow scientists to screen hundreds of disease genes in hundreds of people simultaneously with high accuracy and high efficiency.
Novel Approaches For Activation And Expansion Of Genetically Modified T Cells In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$115,660.00
Summary
Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engi ....Killer T lymphocytes can penetrate tumors and their propagation and transfer into cancer patients has demonstrated some encouraging results, but this form of adoptive immunotherapy remains ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. Our previous work has indicated that killer T lymphocytes can be genetically engineered in culture with tumor recognition receptors. When transferred into mice, these genetically engineered cells can release toxic and inflammatory proteins that cause tumor destruction. In this proposal we wish to further test this approach in mice by enginneering the mouse killer T cells with (i) receptors that provide stronger signals for killing and proliferation; and (ii) with receptors targeting other structures on tumor cells including the tumor vasculature as a means to overcome tumor escape. In addition, we wish to test a novel approach of combining both genetic engineering and vaccination strategies for expanding gene-modified cells after adoptive transfer. These studies will allow the best receptor genes to be transferred to human white blood cells and examined for anti-tumor effects in immune-deficient mice.Read moreRead less
Functions Of FZD7 In The Intestine And Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$644,761.00
Summary
Wnt proteins are a family of signaling molecules that are critical for the function of normal and cancerous epithelial cells in the gut. However, the cell surface receptor that transmits Wnt signals is not known. Our research strongly implicates one Wnt receptor (FZD7). Here we test this using innovative mouse and cell line models. We wish to understand how Wnt-driven processes are activated. This knowledge will lead to novel avenues to block aberrant activation of Wnt signalling in cancer cells
Role Of Immediate Early Gene Induction And AP-1 Activation In HDAC Inhibitor Induced Apoptosis.
Funder
National Health and Medical Research Council
Funding Amount
$524,820.00
Summary
Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with ....Histone deacetylase inhibitors (HDACi) are a novel class of anti-tumor agents, recently approved for the treatment of cutaneous T-cell lymphoma. The goal of this study is to improve our understanding of how this class of drug induces tumor cell death. These studies are designed to provide insight into which patients are most likely to benefit from treatment with these agents. Second, they will provide direction into how the therapeutic efficacy of HDACi may be enhanced, through combination with other existing therapeutics.Read moreRead less
An Integrated Approach For The Efffective Adoptive Immunotherapy Of Cancer
Funder
National Health and Medical Research Council
Funding Amount
$468,119.00
Summary
Killer T lymphocytes can penetrate tumors and their transfer into cancer patients has demonstrated some encouraging results, but this form of immunotherapy remain ineffective in most cancer patients. We propose to improve the tumor trafficking and anti-tumor activities of killer cells by genetically engineering them with proteins that will enable them to recognise and destroy cancer cells. The outcomes of this project will validate this novel approach for treatment of cancer patients.